This study is directed at elucidating the biochemical and physiologic effects associated with peri-ventricular, peri-aqueductal gray stimulation utilized in the therapy of severe, intractable, chronic pain secondary to metastatic cancer without direct central nervous system involvement. Implication of an endogenous opiate system interacting with monoaminergic pathways in the brain stem has been proposed as the substrate for the efficacy of this modality both in experimental animals and in man. The ultimate long range objectives of this study are to evaluate the effect of peri-aqueductal gray stimulation upon chronic pain, CSF and plasma change in levels of B-endorphin, and Met- and Leu-enkephalin utilizing specific radioimmunoassays developed in our laboratory; possible association in diurnal and 24 hour sleep related rhythms in endogenous opiate secretion; changes in 24 hour secretory patterns of human growth hormone, somatostatin, prolactin, follicle stimulating hormone, luteinizing hormone and ACTH; sleep patterns per se and reversibility or blockade of these changes by the specific opiate antagonist, naloxone.